Increasing adipose cell size in the aging rat model of obesity is accompanied by a marked reduction in insulin's ability to stimulate glucose metabolism. Since a fundamental action of insulin in regulating glucose metabolism is its stimulatory effect on glucose transport and since insulin appears to enhance glucose transport by triggering a rapid and reversible translocation of glucose transport systems from a large intracellular pool to the plasma membrane, the effects of increasing cell size on this pool and the translocation process in the isolated adipose cell have been examined in relation to glucose transport activity in the intact cell. With a 10-fold increase in cell size, insulin's ability to stimulate L-arabinose transport in intact cells and to increase the concentration of glucose transport systems in the plasma membrane fraction prepared from these cells practically disappears. At the same time, the basal concentration of glucose transport systems in the low-density microsomal membrane fraction prepared from the enlarged cells is decreased by 80%. Thus, adipose cellular enlargement is accompanied by markedly reduced glucose transport response to insulin which appears to be the consequence of a relative depletion of glucose transport systems in the intracellular pool.